Growth, puberty, and endocrine functions in patients with sporadic or familial neurofibromatosis type 1: a longitudinal study.
ABSTRACT This study prospectively evaluates parameters of growth, puberty, and attained adult height in children with sporadic or familial occurrence of neurofibromatosis type 1 (NF-1), followed up longitudinally, to define the most important factors affecting these parameters.
The study was made up of 89 patients (55 boys, 34 girls) with sporadic (n = 45) or familial NF-1 (13 affected fathers and 31 affected mothers). The average age at referral was 8.9 years (range 8.5-15 years), and the average follow-up period was 8.5 years (6-15 years). A total of 28 patients attained adult height at the time of the report. Anthropometric measurements and bone age determinations were performed at 6- to 12-month intervals. As indicated, central nervous system (CNS) imaging was performed on 60 patients. Serum levels of thyroid stimulating hormone, free T4, lutheinizing hormone, follicle stimulating hormone, testosterone or estradiol, cortisol, and prolactin were measured in all patients periodically, and the pituitary growth hormone reserve was assessed in 32 short patients.
CNS pathology was found in 23 of the 89 patients. A total of 6 patients required neurosurgery, and 2 patients had cranial irradiation. Of these patients, 3 were receiving recombinant growth hormone and thyroxin replacement therapy and 5 patients with precocious puberty were treated with a gonadotropin-releasing hormone analog. All other patients had normal endocrine tests. Precocious puberty was recorded in 5 patients and was more common among the familial cases. The 5 patients with precocious puberty also had CNS pathology. Short stature (<10th percentile) was observed in 25.5% of the patients during the prepubertal period with a significant gradual reduction of their relative height for age (standard scores) during puberty. Short adult height was noted in 12 (43%) of 28 patients, and only 50% of the 28 patients attained an adult height that was appropriate for their respective target height. Short stature was more common among patients with familial NF-1, particularly if the father was affected, and among those patients with CNS pathology. Parental short stature was observed in 39% of the mothers and in 33% of the fathers (59% and 54% among the affected parents, respectively). Tall stature (>90th percentile) was observed in 4 of 89 patients (4.5%), who all had CNS tumors. A highly significant correlation was found among all adult height-predicting parameters (r =.79), and attained adult height was best correlated with the target height (r =.7; n = 28).
Short adult height is an important characteristic of NF-1 and deserves to be emphasized in the evaluation and follow-up of these patients during childhood. Short adult height is strongly linked with familial background of NF-1, in particular if the affected parent is the father, and is affected adversely by the relatively poor pubertal growth. Despite normal pituitary gland and thyroid function tests in most children and adolescents with NF-1, increased incidence of precocious puberty was observed. As the clinical expression in the second generation is more pronounced, the underlying mechanism seems to be mediated by genetic factors that are yet undefined.
- SourceAvailable from: Velibor Tasic[show abstract] [hide abstract]
ABSTRACT: (Full text is available at http://www.manu.edu.mk/prilozi). Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with varied clinical manifestations. The proband is a 6-year-old boy with signs of precocious puberty. His penis was 10 cm, testicles 8 ml, pubic hair P2-3, and the genital skin was hyperpigmented. Multiple cafe au lait spots well above 5 mm were noticeable on his skin, as well as hard subcutaneous nodules, mostly on his trunk. His intelligence and hearing are normal. He has no history of seizures. Laboratory analysis showed: LH LH 1.4 mIU/ml, FSH 6.2 mIU/ml, testosterone 183 ng/ml. Bone age was 9 years. LHRH stimulation was characteristic of true precocious puberty (LH 9.8 mIU/ml and FSH 8.9 mIU/ml after 30 minutes). The MRI of the brain showed a tumor of the suprasellar region with compression of the pituitary stalk. At present the boy is 6 years old and has been treated with triptoreline acetate for 3 months. The volume of the testicles has decreased to 7 ml and a slight loss of pubic hair was noted. In addition, his mother and his grandfather exhibited dermal masses, and focal cutaneous and subcutaneous growths. The great-grand father had had the same cutaneous changes and died at the age of 75 from unrelated causes. It has already been well documented that NF is associated with an increased risk of malignancy and precocious puberty. Hence, we emphasize the need for a close and regular clinical follow-up of the OPT, puberty and patterns of growth. Key words: Neurofibromatosis 1, optic nerve tumor, precocious puberty, familiar occurrence.Prilozi / Makedonska akademija na naukite i umetnostite, Oddelenie za biološki i medicinski nauki = Contributions / Macedonian Academy of Sciences and Arts, Section of Biological and Medical Sciences 12/2010; 31(2):253-9.
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ABSTRACT: The last decades have seen major developments in our knowledge of the different forms of neurofibromatosis (Ferner 2007a, b; Ferner et al. 2007; Friedman et al. 1999; Huson and Hughes 1994; Korf and Rubenstein 2005; North 1997; Ruggieri 2007; Upadhyaya and Cooper 1998a). Evidence based clinical diagnostic criteria and management guidelines have been developed (Baser et al. 2002; Ferner et al. 2007; Gutman et al. 1997; Listernick et al. 1997; Listernick and Charrow 2004a, b; North et al. 1997; Maria 2002; Ruggieri 1999; Wolkenstein et al. 1996). The genes for the two major forms, neurofibromatosis type 1 (NF1) and type 2 (NF2), have been cloned and the gene products, neurofibromin and merlin (also called Schwannomin), respectively, fully characterised (reviewed in Baser et al. 2003, Ferner 2007a, Friedman et al. 1999, Korf and Rubenstein 2005, Upadhyaya and Cooper 1998b).01/2009: pages 51-151;
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ABSTRACT: In consideration of the large number of the rapid advances in this area, it seems appropriate to highlight some of the recent studies that address factors involved in the decision to treat a child with central precocious puberty, and two recent advances in drug therapy. There are still many areas of uncertainty regarding treatment of central precocious puberty, including the hormonal test results that support the diagnosis, the best way to predict adult height, and the effect of the age of the child on the amount of height gained during treatment (adult height minus predicted height). Many studies show that children with onset of symptoms before age 6 benefit the most, but a recent study showed no difference in height benefit between girls initially seen at at least 7 or more than 7 years. Two reports indicate that greater delay from the onset of puberty to the start of therapy with gonadotropin-releasing hormone analogue has a negative effect on adult height. Although there has been considerable experience with monthly injections of gonadotropin-releasing hormone analogues to suppress pubertal development, recent studies show that a slower released formulation given every 3 months is also effective in the majority of patients. The newest form of therapy involves a subcutaneous implant of the gonadotropin-releasing hormone analogue histrelin, which gives excellent gonadotropin suppression for 12 months. Treatment of central precocious puberty continues to be a very active area of clinical investigation, but there are still unresolved questions that future studies will need to address.Current opinion in endocrinology, diabetes, and obesity 03/2009; 16(1):31-6.